To promote research on the interactions of climate change, social instability, and health, we developed a synthetic framework describing potential mechanisms linking distal drivers and proximal triggers that can be used for predictive and explanatory models. At the center of the framework are five interlinked distal drivers that shape local contexts: climate and environmental systems, physical geography, social and economic systems, governance systems, and health systems. Around these are two rings: the inner ring shows contextual factors affecting the baseline risk for instability, and the outer ring displays mechanisms that serve as key proximate triggers or drivers of instability. These rings are separately temporally, with the factors changing the most slowly in the center, followed by stressors, with shocks forming the outermost ring. Multiple factors affect baseline instability, with many potential interactions among distal and proximal factors. Operationally, each of the factors can be considered individually as either driving or mitigating risk in a given setting. This framework can be used to frame interdisciplinary research on the pathways linking these factors and the magnitude, causality, and directionality of relationships across spatial and temperature scales.